Transient regulation of Plasmodium numbers below the density that induces fever has been observed in chronic malaria infections in humans and this species transcending control cannot be explained by immunity alone. Using an in vitro system we have observed density dependent regulation of malaria parasitemia as a mechanism to possibly explain these in vivo observations.
A high parasite density environment induces transcriptional changes and cell death in Plasmodium falciparum blood stages.
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View SamplesTo identify genes regulated by Cav1
Mechanisms through Which Hypoxia-Induced Caveolin-1 Drives Tumorigenesis and Metastasis in Hepatocellular Carcinoma.
Specimen part, Cell line
View SamplesA number of autoimmunity-associated MHC class II proteins interact only weakly with the invariant chain-derived class II-associated invariant chain peptide (CLIP). CLIP dissociates rapidly from I-Ag7 even in the absence of DM, and this property is related to the type 1 diabetes-associated b57 polymorphism. We generated knock-in Non-obese Diabetic (NOD) mice with a single amino acid change in the CLIP segment of invariant chain in order to moderately slow CLIP dissociation from I-Ag7. These knock-in mice had a significantly reduced incidence of spontaneous type 1 diabetes and diminished islet infiltration by CD4 T cells, in particular T cells specific for fusion peptides generated by covalent linkage of proteolytic fragments within b cell secretory granules. Rapid CLIP dissociation enhanced presentation of such extracellular peptides, thus bypassing the conventional MHC class II antigen processing pathway. Autoimmunity-associated MHC class II polymorphisms therefore not only modify binding of self-peptides, but also alter the biochemistry of peptide acquisition. Overall design: Mouse pancreatic tissue was digested by collagenase, and islets were isolated and dissociated into single cells. Beta-cell-specific CD4 T cells were single-cell sorted by FACS based on tetramer labeling, and individual cells were profiled with a modified full length SMART-Seq2 protocol.
Rapid CLIP dissociation from MHC II promotes an unusual antigen presentation pathway in autoimmunity.
Specimen part, Subject
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